Global Splicing Pattern Reversion during Somatic Cell Reprogramming

Ohta, Sho; Nishida, Eisuke; Yamanaka, Shinya; Yamamoto, Takuya

doi:10.1016/j.celrep.2013.09.016

Cited by 58 publications

(81 citation statements)

References 23 publications

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“…Regulated AS has recently emerged as an important event in the control of stem cell pluripotency and somatic cell reprogramming (Gabut et al 2011;Han et al 2013;Ohta et al 2013;Venables et al 2013;Lu et al 2014). Our data suggest that Myc-SAGA-driven expression of a splicing-associated network is critical early in reprogramming to modulate AS events.…”

Section: Gcn5 Is a Coactivator Of The Myc Transcriptional Network In mentioning

confidence: 69%

“…Reprogramming occurs through temporally distinct gene expression phases, known as initiation, maturation, and stabilization (Samavarchi-Tehrani et al 2010;Golipour et al 2012), which involve large-scale changes in the chromatin environment and in patterns of AS (Gabut et al 2011;Polo et al 2012;Han et al 2013;Ohta et al 2013;Sridharan et al 2013;Venables et al 2013). This study uncovers Gcn5 as the primary HAT required during the initiation phase of reprogramming and further implicates three components of the Gcn5-containing SAGA complex (Trrap, Ccdc101, and Taf12) in this process.…”

Section: Discussionmentioning

confidence: 99%

“…S7C). AS of the Slain2 and Plod2 genes was recently described in somatic cell reprogramming and has been implicated in cytoplasmic microtubule elongation and collagen crosslink stabilization, respectively (van der Slot et al 2003;van der Vaart et al 2011;Han et al 2013;Ohta et al 2013;Venables et al 2013). However, the mechanism that contributes to AS of these genes has not been described.…”

Section: Gcn5 Is a Coactivator Of The Myc Transcriptional Network In mentioning

confidence: 99%

“…Furthermore, embryonic stem cells (ESCs) display splicing patterns that are distinct from differentiated cells and critical for maintenance of pluripotency. (Atlasi et al 2008;Rao et al 2010;Salomonis et al 2010;Wu et al 2010;Das et al 2011;Gabut et al 2011;Han et al 2013;Ohta et al 2013;Lu et al 2014). Moreover, step-wise acquisition of ESC AS patterns is critical for successful somatic cell reprogramming (Gabut et al 2011;Han et al 2013;Ohta et al 2013).…”

mentioning

confidence: 99%

“…(Atlasi et al 2008;Rao et al 2010;Salomonis et al 2010;Wu et al 2010;Das et al 2011;Gabut et al 2011;Han et al 2013;Ohta et al 2013;Lu et al 2014). Moreover, step-wise acquisition of ESC AS patterns is critical for successful somatic cell reprogramming (Gabut et al 2011;Han et al 2013;Ohta et al 2013). Although some of the splicing factors that regulate these events-including MBNL, SFRS2, U2af1, and Srsf3-have been uncovered (Han et al 2013;Ohta et al 2013;Lu et al 2014), how these AS regulatory networks are modulated during reprogramming remains to be elucidated.…”

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confidence: 99%

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Myc and SAGA rewire an alternative splicing network during early somatic cell reprogramming

et al. 2015

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Embryonic stem cells are maintained in a self-renewing and pluripotent state by multiple regulatory pathways. Pluripotent-specific transcriptional networks are sequentially reactivated as somatic cells reprogram to achieve pluripotency. How epigenetic regulators modulate this process and contribute to somatic cell reprogramming is not clear. Here we performed a functional RNAi screen to identify the earliest epigenetic regulators required for reprogramming. We identified components of the SAGA histone acetyltransferase complex, in particular Gcn5, as critical regulators of reprogramming initiation. Furthermore, we showed in mouse pluripotent stem cells that Gcn5 strongly associates with Myc and that, upon initiation of somatic reprogramming, Gcn5 and Myc form a positive feed-forward loop that activates a distinct alternative splicing network and the early acquisition of pluripotency-associated splicing events. These studies expose a Myc-SAGA pathway that drives expression of an essential alternative splicing regulatory network during somatic cell reprogramming.

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Section: Gcn5 Is a Coactivator Of The Myc Transcriptional Network In mentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Gcn5 Is a Coactivator Of The Myc Transcriptional Network In mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Myc and SAGA rewire an alternative splicing network during early somatic cell reprogramming

et al. 2015

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Splicing of Pre‐m RNA

Tarn

2015

Encyclopedia of Life Sciences

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The majority of eukaryotic messenger RNAs (m RNAs ) are initially transcribed as intron‐containing precursor m RNAs (pre‐m RNAs ). Removal of introns from each pre‐m RNA by splicing is necessary to generate a mature m RNA . Pre‐m RNA splicing is catalysed by the spliceosome, a large ribonucleoprotein complex that contains five small nuclear RNAs and numerous protein factors and forms anew on each intron of nascent transcripts. In higher eukaryotes, alternative splicing of pre‐m RNA generates multiple m RNA isoforms from a single gene and is regulated by cellular RNA ‐binding proteins. Alternative splicing not only increases proteome diversity but also has the potential to regulate gene expression levels post‐transcriptionally. Thus, alterative splicing may have a great impact on a wide range of physiological and developmental processes. Defects in pre‐m RNA splicing underlie a considerable number of genetic diseases and cancers and may fine‐tune disease severity. Key Concepts In most eukaryotic pre‐mRNAs, the coding sequences (exons) are interrupted by stretches of non‐coding sequences (introns). The spliceosome uses a two‐step transesterification reaction to remove introns and join exons of pre‐mRNAs. The snRNAs and several conserved spliceosomal protein factors are implicated in the key catalytic steps of splicing. Alternative splicing extends proteome diversity and regulates gene expression levels. Alternative splicing is determined by interplay between trans ‐acting regulatory factors and cis ‐elements of pre‐mRNAs. Alteration of cis ‐elements and aberrant control of trans ‐acting factors can lead to diseases.

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Alternative splicing switches: Important players in cell differentiation

Fiszbein

Kornblihtt

2017

BioEssays

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Alternative splicing (AS) greatly expands the coding capacities of genomes by allowing the generation of multiple mature mRNAs from a limited number of genes. Although the massive switch in AS profiles that often accompanies variations in gene expression patterns occurring during cell differentiation has been characterized for a variety of models, their causes and mechanisms remain largely unknown. Here, we integrate foundational and recent studies indicating the AS switches that govern the processes of cell fate determination. We include some distinct AS events in pluripotent cells and somatic reprogramming and discuss new progresses on alternative isoform expression in adipogenesis, myogenic differentiation and stimulation of immune cells. Finally, we cover novel insights on AS mechanisms during neuronal differentiation, paying special attention to the role of chromatin structure.

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Global Splicing Pattern Reversion during Somatic Cell Reprogramming

Cited by 58 publications

References 23 publications

Myc and SAGA rewire an alternative splicing network during early somatic cell reprogramming

Myc and SAGA rewire an alternative splicing network during early somatic cell reprogramming

Splicing of Pre‐m RNA

Alternative splicing switches: Important players in cell differentiation

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